The Marcos Vidal Melo Research Laboratory primarily focuses on understanding, preventing, and treating acute lung injury, especially perioperative lung dysfunction and injury. Ultimately, our aim is to improve the outcomes of surgical and critically ill patients. Functional lung imaging methods are particularly developed and used in our laboratory as they allow us to study in vivo the development of those disease conditions. Imaging techniques are applied to quantify the spatial distribution of tissue density, alveolar volume, ventilation, perfusion, tissue strain, and inflammatory markers in health and disease in experimental models and humans. Using those methods, we have advanced the understanding of regional lung injury in surgical and critical care conditions, and developed methods of prevention and treatment. Our research includes studies in normal lungs, ventilator-induced and endotoxemic lung injury, and acute respiratory distress syndrome in vivo (e.g., humans, large animals, and rodents) and ex vivo (e.g., precision-cut lung slices). We conduct these studies with high level of endophenotyping for pulmonary structure and function using positron emission tomography and high-resolution respiratory gated computed tomography. We have recently expanded our interests to basic-translational research to explore the association of regional dysfunction to local lung genomics and proteomics during acute lung injury.
Research
Our interdisciplinary team of physicians and engineers has developed advanced imaging methods and modalities that allow us to study a wide range of respiratory diseases and conditions in humans and large animals. Combining positron-emission tomography (PET) and computed tomography (CT) allows for both structural assessments using the high spatial resolution of CT and functional assessments using the excellent sensitivity of PET scanners for tracers and their kinetics.
Examples of innovations in imaging from our group include a highly accurate and unique technique of ventilation and perfusion imaging using the 13N-Nitrogen bolus-injection method. We have also developed a patented method for calibrated image-derived input functions relevant for 18F-FDG kinetics, and a novel method for the assessment of the extravascular-extracellular volume in the lungs under conditions of regional edema and alveolar flooding.
Using quantitative PET-CT imaging, we have studied a substantial range of lung diseases and conditions including acute respiratory distress syndrome (ARDS), asthma, chronic obstructive pulmonary disease (COPD), healthy subjects, pulmonary embolism, smoking, and ventilator-induced lung injury (VILI). The assessments in these studies included ventilation, perfusion, strain, 18F-FDG uptake linked to pulmonary inflammation, tissue volume, gas volume, gas fraction, blood volume, and other parameters characterizing disease-specific deviations from healthy conditions.
Our laboratory aims to understand the fundamental mechanisms of lung injury associated with lung heterogeneity and integrate findings in basic biology with clinical medicine. Our research is currently focused on:
- lung injury associated with pulmonary atelectasis or lung collapse, including two major important aspects - inflammatory response and alveolar-capillary barrier function - in different clinical settings such as with or without systemic inflammation induced by endotoxin (lipopolysaccharide);
- the correlation between lung injury and different levels of strain associated with mechanical ventilation with or without additional systemic inflammation;
- the relevance of cyclic pulmonary capillary closure during mechanical ventilation for lung injury with particular attention to endothelial damage.
Our laboratory will utilize a repertoire of relevant lung injury models in vivo (e.g., large animal such as sheep or pig, and rodent such as mouse or rat) and ex vivo (e.g., precision-cut lung slices (PCLSs) from mice or human bio-samples) as well as molecular genetic approaches to examine the potential responses of the lung to different mechanical irritants. Our research encompasses multiple disciplines including basic, translational, and clinical sciences, to uncover or identify novel and efficient therapeutic targets for lung injury such as ARDS and VILI.
